LAUSR

INTRODUCTION AND OBJECTIVE: Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is the gold-standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), while over 30% patients experience tumor recurrence following BCG therapy. We aimed to screen for reliable circulating cytokines/chemokines to predict and monitor BCG treatment outcome. METHODS: In this prospective, longitudinal study, serum samples were collected before and during each cycle of BCG induction therapy from 2 successive recruited cohorts. We used a 48 cytokines/ chemokines Bio-Plex multiplex assay to screen potential BCG failurerelated serum cytokines/chemokines in discovery cohort. After screening, the most valuable cytokine was further quantified with ELISA in validation cohort. We analyzed the correlation between the level of selected cytokine and the density of different immune cells, and explored its possible mechanism following BCG therapy. RESULTS: After screening of 78 serum samples from 13 patients in discovery cohort, we identified CCL27 as a potential novel marker for predicting BCG response. In validation cohort, we found that baseline serum CCL27 >119.6 pg/mL was the best predictor of recurrence-free survival, providing 79% sensitivity, 86% specificity. The combination predictive value of serum CCL27 at all 6 time points during induction therapy had an AUC value of 0.901. Furthermore, we found serum CCL27 strongly correlated with Tregs in situ. CCL27 could promote the migration of CCR10þ Tregs to TME, thereby shortening disease recurrence survival following BCG therapy. CONCLUSIONS: Serum CCL27 could be a practical and reliable marker to predict and monitor the response of BCG immunotherapy. Our results underline the CCL27/CCR10/Treg axis as a potential treatment target for patients with BCG failure.